The 6-month interim results from the Verteporfin Intravitreal Triamcinolone Acetonide Study indicate that the combination of photodynamic therapy with verteporfin and either pegaptanib (Macugen, OSI/Eyetech and Pfizer Ophthalmics) or triamcinolone acetonide (Kenalog, Bristol-Myers Squibb) in two different doses resulted in no differences among the groups on several key measures.
These measures included the primary end point of a vision loss of fewer than 15 letters, the mean change in visual acuity (VA), and the degree of change in lesion size. Peter K. Kaiser, MD, reported the results at the Association for Research in Vision and Ophthalmology annual meeting.
"The rationale for combining PDT with either a steroid or an antiangiogenic drug is that verteporfin can be used to close the choroidal neovascularization (CNV)," said Dr. Kaiser, director, Clinical Research Center, Cole Eye Institute, Cleveland Clinic, Cleveland. "Then, either an antiangiogenic drug can be used to prevent angiogenesis and recurrence after the damage caused by PDT, or a steroid can be used to inhibit inflammation from disrupting the blood-retinal barrier after PDT. VA can be improved over PDT alone using combination treatment of PDT and steroids. This was the impetus behind the VERITAS study."
The inclusion criteria included subfoveal CNV caused by age-related macular degeneration (AMD), patient age of more than 50 years, a best-corrected VA letter score of 73 to 24 (Snellen equivalent, 20/40 to 20/320), CNV equivalent to 50% or more of the total lesion area, any CNV lesion composition, a greatest linear dimension of 5,400 µm or less, recent disease progression in those lesions with occult and no classic CNV, and no previous treatment of the subfoveal lesions.
The patients were evaluated by fluorescein angiography at 3-month intervals. If leakage was observed, then PDT also was applied at 3-month intervals. In the two groups treated with triamcinolone, the patients were examined at 6-week intervals and received a sham injection. They were reexamined using fluorescein angiography at 3-month intervals; if leakage was observed at the 3-month examination, then they were treated with combination therapy of PDT and triamcinolone, he explained.
Because of the release of ranibizumab (Lucentis, Genentech), the study enrollment was stopped before the planned 339 patients were enrolled; a total of 111 patients were included in the prospective randomized, double-masked, multicenter clinical trial, according to Dr. Kaiser.
"Originally, the study was powered to show an 80% difference to detect a 7.5-letter difference at 6 months," he said. "Because of the halting of the study, the power decreased to 43%."
In addition to the decreased power of the study, the baseline demographics showed a significant difference among the treatment groups in the mean VA at baseline between the PDT and ranibizumab group and the PDT with the low-dose triamcinolone group. In the triamcinolone group, there were more patients with cataract compared with the ranibizumab group. The low-dose triamcinolone group had more patients with minimally classic lesions, the ranibizumab group included more patients with predominantly classic lesions, and the high-dose triamcinolone group had more patients with occult lesions.
"Regarding the primary end point, loss of fewer than 15 letters of VA, there was no significant difference among the groups. All three study groups lost VA at the 6-month examination, and there was no significant difference in the mean and median VA losses among the groups," Dr. Kaiser reported. He pointed out that the VA loss was less than in the initial clinical studies of PDT, but the study groups are not comparable.
About 50% to 60% of patients in the VERITAS trial had stable or increased VA, but this was not the same as with ranibizumab.